Fruzaqla

Clinical summary

Indications and usage 1. INDICATIONS AND USAGE FRUZAQLA is indicated for the treatment of adult patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine‑, oxaliplatin‑, and irinotecan‑based chemotherapy, an anti‑VEGF therapy, and, if RAS wild‑type and medically appropriate, an anti-EGFR therapy. FRUZAQLA is a kinase inhibitor indicated for the treatment of adult patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine‑, oxaliplatin‑, and irinotecan‑based chemotherapy, an anti‑VEGF therapy, and, if RAS wild‑type and medically appropriate, an anti-EGFR therapy. ( 1 ) Dosage and administration 2. DOSAGE AND ADMINISTRATION The recommended dose of FRUZAQLA is 5 mg orally once daily, with or without food for the first 21 days of each 28-day cycle. ( 2.1 ) 2.1. Recommended Dosage The recommended dose of FRUZAQLA is 5 mg orally once daily for the first 21 days of each 28-day cycle until disease progression or unacceptable toxicity. Take FRUZAQLA with or without food [see Clinical Pharmacology (12.3) ] at approximately the same time each day. Swallow the FRUZAQLA capsule whole. Take a missed dose if less than 12 hours have passed since the missed scheduled dose. Do not take two doses on the same day to make up for a missed dose. Do not take an additional dose if vomiting occurs after taking FRUZAQLA but continue with the next scheduled dose. 2.2. Dosage Modifications for Adverse Reactions The recommended dose reductions for adverse reactions are provided in Table 1. Table 1: Recommended Dose Reductions for FRUZAQLA Dose Level FRUZAQLA Dosage First dose reduction 4 mg orally once daily Second dose reduction 3 mg orally once daily Permanently discontinue FRUZAQLA in patients unable to tolerate 3 mg orally once daily. The recommended dosage modifications for adverse reactions are provided in Table 2. Table 2: Recommended Dosage Modifications for FRUZAQLA Adverse Reaction Severity Severity as defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. FRUZAQLA Dosage Modification Hypertension [see Warnings and Precautions (5.1) ] Grade 3 Withhold FRUZAQLA for Grade 3 hypertension that persists despite optimal anti-hypertensive therapy. If hypertension fully resolves or recovers to Grade 1, resume at the next lower dose level. Grade 4 Permanently discontinue FRUZAQLA. Hemorrhagic Events [see Warnings and Precautions (5.2) ] Grade 2 Withhold FRUZAQLA until bleeding fully resolves or recovers to Grade 1. Resume at the next lower dose level. Grade 3 or Grade 4 Permanently discontinue FRUZAQLA. Hepatotoxicity [see Warnings and Precautions (5.5) ] Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times upper limit of normal (ULN), or greater than 3 times baseline if baseline was abnormal; or bilirubin greater than 1.5 times ULN, or greater than 1.5 times baseline if baseline was abnormal Withhold FRUZAQLA and monitor AST, ALT and total bilirubin until resolution to Grade 1 or baseline. Resume at the next lower dose level. ALT or AST greater than 3 times ULN with concurrent total bilirubin greater than 2 times ULN (in the absence of cholestasis or hemolysis) Permanently discontinue FRUZAQLA. AST or ALT greater than 20 times ULN if baseline was normal, or greater than 20 times baseline if baseline was abnormal; or bilirubin greater than 10 times ULN if baseline was normal, or greater than 10 times baseline if baseline was abnormal Permanently discontinue FRUZAQLA. Proteinuria [see Warnings and Precautions (5.6) ] 2 grams or greater proteinuria in 24 hours Withhold FRUZAQLA until proteinuria fully resolves or is <1 gram/24 hours. Upon recovery, resume at the next lower dose level. Permanently discontinue FRUZAQLA for nephrotic syndrome or if proteinuria does not recover to <1 gram/24 hours. Palmar-plantar erythrodysesthesia (PPE) [see Warnings and Precautions (5.7) ] Grade 2 Withhold FRUZAQLA and initiate supportive treatment. If toxicity fully resolves or recovers to Grade 1, resume at the same dose level. Grade 3 Withhold FRUZAQLA and initiate supportive treatment. If toxicity fully resolves or recovers to Grade 1, resume at the next lower dose level. Other Adverse Reactions [see Adverse Reactions (6.1) ] Grade 3 Withhold FRUZAQLA. If toxicity fully resolves or recovers to Grade 1, resume at the next lower dose level. Grade 4 Discontinue FRUZAQLA. Consider resuming FRUZAQLA at the next lower dose level only if the toxicity is non-life threatening and fully resolves or recovers to Grade 1 and the potential benefit outweighs the risks. Warnings and cautions 5. WARNINGS AND PRECAUTIONS Hypertension: Control blood pressure prior to treatment and monitor during treatment. Manage with anti-hypertensive medications and adjustment of the dose of FRUZAQLA, if necessary. Withhold, dose reduce, or permanently discontinue based on severity of hypertension. ( 2.